Altered aquaporin expression in glaucoma eyes

Abstract

Aquaporins (AQP) are channels in the cell membrane that mainly facilitate a passive transport of water. In the eye, AQPs are expressed in the ciliary body and retina and may contribute to the pathogenesis of glaucoma and optic neuropathy. We investigated the expression of AQP1, AQP3, AQP4, AQP5, AQP7 and AQP9 in human glaucoma eyes compared with normal eyes. Nine glaucoma eyes were examined. Of these, three eyes were diagnosed with primary open angle glaucoma; three eyes had neovascular glaucoma; and three eyes had chronic angle-closure glaucoma. Six eyes with normal intraocular pressure and without glaucoma were used as control. Immunohistochemistry was performed using antibodies against AQP1, AQP3, AQP4, AQP5, AQP7 and AQP9. For each specimen, optical densities of immunoprecipitates were measured using Photoshop and the staining intensities were calculated. Immunostaining showed labelling of AQP7 and AQP9 in the nonpigmented ciliary epithelium and the staining intensities were significantly decreased in glaucoma eyes (p = 0.003; p = 0.018). AQP7 expression in the Müller cell endfeet was increased (p = 0.046), and AQP9 labelling of the retinal ganglion cells (RGC) showed decreased intensity (p = 0.037). No difference in AQP1, AQP4 and AQP9 expression was found in the optic nerve fibres. This study is the first investigating AQPs in human glaucoma eyes. We found a reduced expression of AQP9 in the retinal ganglion cells of glaucoma eyes. Glaucoma also induced increased AQP7 expression in the Müller cell endfeet. In the ciliary body of glaucoma eyes, the expression of AQP7 and AQP9 was reduced. Therefore, the expression of AQPs seems to play a role in glaucoma.

Glia–neuron interactions in the mammalian retina

“…Alternatively, the expression of both AQP7 and AQP9 is reduced in the ciliary body of glaucomatous eyes. Therefore, AQP expression seems to play some role in glaucoma (Tran et al, 2014).…”

Glaucoma: the retina and beyond

“…The dysregulation of the production and clearance of cytotoxic compounds, such as Aβ, coupled with recent postulations as to the existence of an ocular glymphatic system [40], has led to the development of a novel hypothesis for glaucoma pathology based on the reduction in CSF clearance from the SAS via ocular glymphatic dysregulation [189]. Therapeutic interventions to increase glymphatic clearance such as aquaporins agonists, which are currently under investigation for the treatment of AD, may also be of interest for the treatment of glaucoma [174]. Finally, the recognition that Schlemm’s canal is a VEGF-c responsive vessel with lymphatic phenotype [5], coupled with the observation that the concentration of proteins implicated in cytotoxic processes (inflammation, apoptosis, angiogenesis, and oxidative stress) in the aqueous humour that are elevated in ocular disease [9] may suggest a role for aqueous outflow in the removal of cytotoxic compounds from posterior ocular tissues.…”

Aqp9 Gene Deletion Enhances Retinal Ganglion Cell (RGC) Death and Dysfunction Induced by Optic Nerve Crush: Evidence that Aquaporin 9 Acts as an Astrocyte-to-Neuron Lactate Shuttle in Concert with Monocarboxylate Transporters To Support RGC Function and Survival

“…Catecholaminergic amacrine cells were the first reported cells in the retina to express AQP9 [ 10 ]). Subsequent studies by our group [ 11 , 12 ] and others [ 13 ] identified that RGCs also express AQP9. In addition, it has been reported that elevated intraocular pressure (IOP) and optic nerve transection in rodents [ 11 , 12 ], and glaucoma in humans [ 13 ], lead to reduced AQP9 expression in RGCs.…”